1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline | 909909-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 菲咯啉
• 英文名称: 1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline
• 英文别名: (10bS)-1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline；(4aR,10bS)-1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline
• CAS: 909909-25-7
• 化学式: C₁₂H₁₆N₂
• 分子量: 188.272
• InChiKey: FOPSJTFDPLIFJI-JQWIXIFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline 在 copper(l) iodide 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 、 N,N'-二甲基乙二胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 4-((R)-3-(((4aR,10bS)-3,4,4a,5,6,10b-hexahydro-1,10-phenanthrolin-1(2H)-yl)methyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)morpholin-3-one
  参考文献：
  名称：

  [EN] CXCR4 MODULATORS AND USES RELATED THERETO
  [FR] MODULATEURS DE CXCR4 ET LEURS UTILISATIONS

  摘要：

  CXCR4 antagonists and pharmaceutical formulations thereof are disclosed. The compounds and pharmaceutical formulations disclosed herein can be used to antagonize the CXCR4 pathway for mobilizing stem cells or treating a condition, disorder, or disease associated with the CXCR4 pathway. Exemplary conditions, disorders, and diseases relevant to this disclosure include HIV infections, WHIM syndrome, Waldenström macroglobulinemia, chronic neutropenia, primary immune-deficiency, aplastic anemia, hypoplastic myelodysplastic syndrome, acute respiratory distress syndrome (ARDS), ankylosing spondylitis, autoimmune diseases, and cancers.

  公开号：

  WO2023003862A1
• 作为产物：
  描述：

  (4aS,10bR)-1-{(1S)-1-[4-(methyloxy)phenyl]ethyl}-1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以98%的产率得到1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline
  参考文献：
  名称：

  具有抗HIV-1活性的新型三环1,2,3,4,4a，5,6,10b-八氢-1,10-菲咯啉环系统和CXCR4拮抗剂的合成

  摘要：

  描述了新的1,2,3,4,4a，5,6,10b-八氢-1,10-菲咯啉环系统的立体异构和非对映选择性合成。制备了所有四种非对映异构体的衍生物，并在> 98％ee中分离。比较纯对映异构体，以确定最佳抗HIV活性所需的优选绝对和相对构型。介绍了新合成的三环八氢菲咯啉抑制剂的抗HIV效能和药代动力学特性，并与先前报道的双环（8 S）-N-甲基-5,6,7,8-四氢-8-喹啉胺类似物进行了比较。

  DOI：

  10.1016/j.bmcl.2010.02.030

文献信息

• [EN] CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR CXCR4 DE CHIMIOKINE ET LEURS UTILISATIONS
  申请人：UNIV EMORY

  公开号：WO2018156595A1

  公开（公告）日：2018-08-30

  The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used for managing CXCR4 related conditions, typically prevention or treatment of viral infections abnormal cellular proliferation, retinal degeneration, inflammatory diseases, or as an immunostimulant or immunosuppressant or for managing cancer and may be administered with another active ingredient such as an antiviral agent or chemotherapeutic agent.

  该披露涉及趋化因子CXCR4受体调节剂及其相关用途。这些受体调节剂可以配制成包含所披露的化合物或其药学上可接受的盐或前药的药物组合物。这些组合物可用于管理与CXCR4相关的疾病，通常用于预防或治疗病毒感染、异常细胞增殖、视网膜退化、炎症性疾病，或作为免疫刺激剂或免疫抑制剂，或用于癌症管理，并可与另一种活性成分一起给药，如抗病毒药物或化疗药物。
• Chemical Compounds
  申请人：Gudmundsson Kristjan

  公开号：US20090093454A1

  公开（公告）日：2009-04-09

  The present invention provides compounds of Formula (I) comprising: including salts, solvates, and physiologically functional derivatives thereof, pharmaceutical formulations containing them, processes for their preparation, and methods of treatment using them.

  本发明提供了式（I）的化合物，包括盐、溶剂化合物和生理功能衍生物，以及含有它们的制药配方、它们的制备过程和使用它们的治疗方法。
• WO2006/96444
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Pharmacological Evaluation of Second-Generation Tetrahydroisoquinoline-Based CXCR4 Antagonists with Favorable ADME Properties
  作者：Huy H. Nguyen、Michelle B. Kim、Robert J. Wilson、Christopher J. Butch、Katie M. Kuo、Eric J. Miller、Yesim A. Tahirovic、Edgars Jecs、Valarie M. Truax、Tao Wang、Chi S. Sum、Mary E. Cvijic、Gretchen M. Schroeder、Lawrence J. Wilson、Dennis C. Liotta

  DOI：10.1021/acs.jmedchem.8b00450

  日期：2018.8.23

  CXCR4 is a G-protein-coupled receptor that interacts with its cognate ligand, CXCL12, to synchronize many physiological responses and pathological processes. Disruption of the CXCL12-CXCR4 circuitry by small-molecule antagonists has emerged as a promising strategy for cancer intervention. We previously disclosed a hit-to-lead effort that led to the discovery of a series of tetrahydroisoquinoline-based CXCR4 antagonists exemplified by the lead compound TIQ15. Herein, we describe our medicinal-chemistry efforts toward the redesign of TIQ15 as a result of high mouse-microsomal clearance, potent CYP2D6 inhibition, and poor membrane permeability. Guided by the in vitro ADME data of TIQ15, structural modifications were executed to provide compound 12a, which demonstrated a reduced potential for first-pass metabolism while maintaining CXCR4 potency. Subsequent SAR studies and multiparameter optimization of 12a resulted in the identification of compound 25o, a highly potent, selective, and metabolically stable CXCR4 antagonist possessing good intestinal permeability and low risk of CYP-mediated drug-drug interactions.
• CHEMICAL COMPOUNDS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1853604A2

  公开（公告）日：2007-11-14